Increased thalamocortical functional connectivity on discontinuation of treatment in painful diabetic peripheral neuropathy

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posted on 2024-06-21, 16:57 authored by Gordon Sloan, Kevin Teh, Sharon Caunt, Iain Wilkinson, Dinesh Selvarajah, Solomon Tesfaye

Abstract

Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy (Painful-DPN). However, the impact of neuropathic pain treatment on functional connectivity has not been investigated. Sixteen participants underwent resting state functional MRI (rs-fMRI) when optimally treated for neuropathic pain during their involvement in the OPTION-DM trial and 1-week following withdrawal of treatment. On discontinuation of pain treatment, there was a rise in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and neuropathy pain symptom inventory). Moreover, when participants were stratified into higher and lower than average baseline pain sub-groups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower baseline pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials.

Article Highlights

· Why did we undertake the study? Functional connectivity alterations have been found in the brain in painful diabetic neuropathy (Painful-DPN), but the impact of treatment on these measures is unknown.

· What is the specific question we wanted to answer? Will functional connectivity between key pain processing brain regions rise on withdrawal of treatment?

· What did we find? Discontinuation of neuropathic pain treatment leads to increasesin functional connectivity between the thalamus and primary somatosensory and insular cortices.

· What are the implications of our findings? Cerebral functional connectivity demonstrate the potential to act as objective biomarkers for Painful-DPN in clinical trials.